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181.
Akira Wagatsuma Yuzo Takayama Takayuki Hoshino Masataka Shiozuka Shigeru Yamada Ryoichi Matsuda Kunihiko Mabuchi 《Molecular and cellular biochemistry》2018,437(1-2):45-53
Endothelial inflammation and monocyte plays an essential role in the initiation and progression of atherosclerosis. Ghrelin is beneficial for atherosclerosis progression. However, the detailed and precise molecular mechanisms of how ghrelin regulates endothelial inflammation are not clear. In this study, we investigated the regulation mechanism of ghrelin on TNF-α-activated endothelial inflammation and monocyte adhesion. It was found that TNF-α-induced monocyte adhesion on HUVEC was significantly attenuated by ghrelin. Furthermore, we found that ghrelin effectively suppressed TNF-α-induced inflammatory factors’ (including ICAM-1, VCAM-1, MCP-1, and IL-1β) expression through inhibiting AMPK phosphorylation and p65 expression both in HUVEC and THP-1. This phenomenon was further demonstrated by using AMPK agonist AICAR and inhibitor compound C, respectively. Our findings suggest that ghrelin may mediate TNF-α-induced endothelial inflammation and monocyte adhesion, in part via AMPK/NF-κB signaling pathway. These novel anti-inflammatory and immunoregulatory actions of ghrelin may play a certain role in understanding the formation and development of atherosclerosis. 相似文献
182.
183.
Although many chemotherapeutic strategies against cancer have been developed, pancreatic cancer is one of the most aggressive and intractable types of malignancies. Therefore, new strategies and anti-cancer agents are necessary to treat this disease. Metformin is a widely used drug for type-2 diabetes, and is also known as a promising candidate anti-cancer agent from recent studies in vitro and in vivo. However, the mechanisms of metformin’s anti-cancer effects have not been elucidated. We demonstrated that metformin suppressed the expression of miR-221, one of the most well-known oncogenic microRNAs, in human pancreatic cancer PANC-1 cells. Moreover, we showed that the down-regulation of miR-221 by metformin caused G1-phase arrest via the up-regulation of p27, one of the direct targets of miR-221. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is also a promising agent for cancer treatment. While recent studies showed that treatment with only TRAIL was not effective against pancreatic cancer cells, the present data showed that metformin sensitized p53-mutated pancreatic cancer cells to TRAIL. Metformin induced the expressions of death receptor 5 (DR5), a receptor for TRAIL, and Bim with a pro-apoptotic function in the downstream of TRAIL-DR5 pathway. We suggest that the up-regulation of these proteins may contribute to sensitization of TRAIL-induced apoptosis. The combination therapy of metformin and TRAIL could therefore be effective in the treatment of pancreatic cancer. 相似文献
184.
185.
Ryoichi Yokoyama Takayuki Nozawa Hikaru Takeuchi Yasuyuki Taki Atsushi Sekiguchi Rui Nouchi Yuka Kotozaki Seishu Nakagawa Carlos Makoto Miyauchi Kunio Iizuka Takamitsu Shinada Yuki Yamamoto Sugiko Hanawa Tsuyoshi Araki Hiroshi Hashizume Keiko Kunitoki Mayu Hanihara Yuko Sassa Ryuta Kawashima 《PloS one》2015,10(3)
When faced with a problem or choice, humans can use two different strategies: “cognitive reflectivity,” which involves slow responses and fewer mistakes, or “cognitive impulsivity,” which comprises of quick responses and more mistakes. Different individuals use these two strategies differently. To our knowledge, no study has directly investigated the brain regions involved in reflectivity–impulsivity; therefore, this study focused on associations between these cognitive strategies and the gray matter structure of several brain regions. In order to accomplish this, we enrolled 776 healthy, right-handed individuals (432 men and 344 women; 20.7 ± 1.8 years) and used voxel-based morphometry with administration of a cognitive reflectivity–impulsivity questionnaire. We found that high cognitive reflectivity was associated with greater regional gray matter density in the ventral medial prefrontal cortex. Our finding suggests that this area plays an important role in defining an individual’s trait associated with reflectivity and impulsivity. 相似文献
186.
Zhaoqiu Zheng Cong Huang Yinting Guo Kaijun Niu Haruki Momma Yoritoshi Kobayashi Shin Fukudo Ryoichi Nagatomi 《PloS one》2015,10(3)
Background
Carbohydrates can cause gastrointestinal symptoms due to incomplete absorption in the small bowel. Thus, high-carbohydrate diets may induce symptoms of irritable bowel syndrome (IBS).Objective
This observational and cross-sectional study assessed the association between consumption of several carbohydrate-enriched staple foods, such as rice, Japanese wheat noodles, Chinese noodles, bread, pasta, and buckwheat noodles, and the prevalence of IBS in Japanese adults.Subjects and Methods
One thousand and eighty-two (837 men) Japanese adult employees aged 19-85 were included in this cross-sectional study conducted in 2011. IBS diagnosis was based on the Rome III criteria. Consumption of staple foods was assessed using a brief self-administered diet history questionnaire, and divided into three categories (low, middle, high) depending on their distribution.Results
In the multivariate analysis, daily consumption of rice (odds ratios [ORs] and [95% confidence interval (CI)]: middle, 1.36 [0.93–1.99]; high, 1.67 [1.12–2.49]; P for trend = 0.01), bread (middle, 1.88 [1.28–2.75]; high, 1.63 [1.10–2.41]; P for trend = 0.01), pasta (middle, 1.47 [1.01–2.15]; high, 1.68 [1.12–2.52]; P for trend = 0.01), and buckwheat noodles (middle, 1.76 [1.18–2.61]; high, 1.98 [1.31–3.00]; P for trend = 0.001) were associated with higher prevalence of IBS after adjustment for socio-demographic, anthropometric, and lifestyle-related factors. Buckwheat noodles, but not other staple foods, retained an association with the prevalence of IBS even after adjustment for daily intake of carbohydrates or plant proteins.Conclusions
This cross-sectional study demonstrated that the consumption of staple foods, such as rice, bread, pasta, and buckwheat noodles is associated with the prevalence of IBS. Of these, the consumption of buckwheat noodles, but not other staple foods, is associated with IBS independent of carbohydrate or plant protein contents. 相似文献187.
188.
Christopher M. Allan Shauna Hill Susan Morvaridi Ryoichi Saiki Jarrett S. Johnson Wei-Siang Liau Kathleen Hirano Tadashi Kawashima Ziming Ji Joseph A. Loo Jennifer N. Shepherd Catherine F. Clarke 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(4):776-791
Coenzyme Qn (ubiquinone or Qn) is a redox active lipid composed of a fully substituted benzoquinone ring and a polyisoprenoid tail of n isoprene units. Saccharomyces cerevisiae coq1–coq9 mutants have defects in Q biosynthesis, lack Q6, are respiratory defective, and sensitive to stress imposed by polyunsaturated fatty acids. The hallmark phenotype of the Q-less yeast coq mutants is that respiration in isolated mitochondria can be rescued by the addition of Q2, a soluble Q analog. Yeast coq10 mutants share each of these phenotypes, with the surprising exception that they continue to produce Q6. Structure determination of the Caulobacter crescentus Coq10 homolog (CC1736) revealed a steroidogenic acute regulatory protein-related lipid transfer (START) domain, a hydrophobic tunnel known to bind specific lipids in other START domain family members. Here we show that purified CC1736 binds Q2, Q3, Q10, or demethoxy-Q3 in an equimolar ratio, but fails to bind 3-farnesyl-4-hydroxybenzoic acid, a farnesylated analog of an early Q-intermediate. Over-expression of C. crescentus CC1736 or COQ8 restores respiratory electron transport and antioxidant function of Q6 in the yeast coq10 null mutant. Studies with stable isotope ring precursors of Q reveal that early Q-biosynthetic intermediates accumulate in the coq10 mutant and de novo Q-biosynthesis is less efficient than in the wild-type yeast or rescued coq10 mutant. The results suggest that the Coq10 polypeptide:Q (protein:ligand) complex may serve essential functions in facilitating de novo Q biosynthesis and in delivering newly synthesized Q to one or more complexes of the respiratory electron transport chain. 相似文献
189.
Ryoichi Ban Kimitaka Takitani Han-Suk Kim Takuji Murata Takao Morinobu Tohru Ogihara 《Free radical research》2013,47(9):933-938
f -Tochopherol transfer protein ( f TTP), a 32 kDa protein exclusively expressed in liver cytosol, has a high binding affinity for f -tochopherol. The factors that regulate the expression of hepatic f TTP are not clearly understood. In this study, we investigated whether or not exposure to hyperoxia (>95% O 2 for 48 h) could alter the expression of hepatic f TTP. We also examined the association between the expression of antioxidant enzymes (hepatic glutathione peroxidase (GPX) and Mn-superoxide dismutase (Mn-SOD)) and the expression of hepatic f TTP. The levels of thiobarbituric acid-reactive substances (TBARS) in both plasma and liver were significantly higher after rats were exposed to hyperoxia for 48 h when compared with the levels in control rats. Northern blotting showed a decrease in the expression of f TTP messenger RNA (mRNA) after hyperoxia, although the f TTP protein level remained constant. Expression of Mn-SOD mRNA and protein, as well as the expression of GPX mRNA, were stable after hyperoxia. These findings indicate that mRNA for hepatic f TTP, rather than Mn-SOD or GPX, may be highly responsive to oxidative stress. 相似文献
190.
Tomoaki Inoue Kunihisa Kobayashi Toyoshi Inoguchi Noriyuki Sonoda Yasutaka Maeda Eiichi Hirata Yoshinori Fujimura Daisuke Miura Ken-ichi Hirano Ryoichi Takayanagi 《Biochemical and biophysical research communications》2013
Adipose triglyceride lipase (ATGL) was recently identified as a rate-limiting triglyceride (TG) lipase and its activity is stimulated by comparative gene identification-58 (CGI-58). Mutations in the ATGL or CGI-58 genes are associated with neutral lipid storage diseases characterized by the accumulation of TG in multiple tissues. The cardiac phenotype, known as triglyceride deposit cardiomyovasculopathy, is characterized by TG accumulation in coronary atherosclerotic lesions and in the myocardium. Recent reports showed that myocardial TG accumulation is significantly higher in patients with diabetes and is associated with impaired left ventricular diastolic function. Therefore, we investigated the roles of ATGL and CGI-58 in the development of myocardial steatosis in the diabetic state. Histological examination with oil red O staining showed marked lipid deposition in the hearts of diabetic fatty db/db mice. Cardiac triglyceride and diglyceride contents were greater in db/db mice than in db/+ control mice. Next, we determined the expression of genes and proteins that affect lipid metabolism, and found that ATGL and CGI-58 expression levels were decreased in the hearts of db/db mice. We also found increased expression of genes regulating triglyceride synthesis (sterol regulatory element-binding protein 1c, monoacylglycerol acyltransferases, and diacylglycerol acyltransferases) in db/db mice. Regarding key modulators of apoptosis, PKC activity, and oxidative stress, we found that Bcl-2 levels were lower and that phosphorylated PKC and 8-hydroxy-2′-deoxyguanosine levels were higher in db/db hearts. These results suggest that reduced ATGL and CGI-58 expression and increased TG synthesis may exacerbate myocardial steatosis and oxidative stress, thereby promoting cardiac apoptosis in diabetic mice. 相似文献